Abstract：
:We have recently shown that dithiocarbamate (DC) disulfides inhibit proteolytic processing of the caspase-3 proenzyme in Jurkat T lymphocytes treated with anti-CD95 (Fas/APO-1) antibody. Because the processing can be accomplished by caspase activity, we investigated the effect of DC disulfides, such as disulfiram (DSF), on active caspases. DSF showed a dose-dependent inhibition was prevented by including dithiothreitol (DTT) in the reaction buffer, thiol-disulfide exchange between inhibitor and target is suggested. Direct interaction of DSF with caspases was confirmed by its inhibition of the purified Ac-DEVD-AMC cleaving protease, caspase-3 (CPP32/apopain). An apparent rate constant (K(app)) for this inhibition was estimated to be 0.45 x 10(3)M(-1)s(-1). DSF was also observed to inhibit the purified Ac-YVAD-AMC cleaving enzyme, caspase-1 (interleukin-1 beta-converting enzyme, ICE), with a K(app) of 2.2 x 10(3) M(-1)s(-1). In this case protein mixed disulfide formation between DSF and caspase-1 was directly demonstrated using 35S-labeled DSF. The physiological disulfide GSSG was also observed to influence the activity of caspases. A glutathione buffer (5 mM) with a GSH:GSSG ratio of 9:1 decreased the Ac-DEVD-AMC cleaving activity in S100 cytosolic extracts by 50% as compared to GSH controls without GSSG. In conclusion, our study shows that caspases are quite sensitive to thiol oxidation and that DSF is a very potent oxidant of caspase protein thiol(s), being 700-fold more potent than glutathione disulfide.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Nobel CS,Kimland M,Nicholson DW,Orrenius S,Slater AFdoi
10.1021/tx970131msubject
Has Abstractpub_date
1997-12-01 00:00:00pages
1319-24issue
12eissn
0893-228Xissn
1520-5010pii
tx970131mjournal_volume
10pub_type
杂志文章abstract：:Enzyme-linked immunosorbent assays (ELISAs) are reported for the detection of atrazine and its principle metabolite in human urine. The ELISAs can be used with crude urine or following extraction and partial purification by methods described in this report. GC, MS, and HPLC techniques were used to confirm and compleme...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
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journal_title：Chemical research in toxicology
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journal_title：Chemical research in toxicology
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journal_title：Chemical research in toxicology
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journal_title：Chemical research in toxicology
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journal_title：Chemical research in toxicology
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00028a013
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journal_title：Chemical research in toxicology
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00031a008
更新日期：1993-01-01 00:00:00
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更新日期：1989-05-01 00:00:00
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更新日期：2005-07-01 00:00:00
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pub_type： 杂志文章
doi：10.1021/acs.chemrestox.9b00228
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journal_title：Chemical research in toxicology
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更新日期：2001-11-01 00:00:00
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journal_title：Chemical research in toxicology
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
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journal_title：Chemical research in toxicology
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更新日期：2004-11-01 00:00:00
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journal_title：Chemical research in toxicology
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更新日期：2014-04-21 00:00:00
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更新日期：2015-05-18 00:00:00
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journal_title：Chemical research in toxicology
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更新日期：2004-12-01 00:00:00
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journal_title：Chemical research in toxicology
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journal_title：Chemical research in toxicology
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx960201+
更新日期：1997-04-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
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更新日期：1997-06-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00042a008
更新日期：1994-11-01 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx010029w
更新日期：2001-09-01 00:00:00
